Weinreb Ketone Synthesis

The reaction of esters and carboxylic acid chlorides with organolithium
and organomagnesium compounds does not lead to ketones in high yields,
because the intermediate ketones are still highly reactive toward the
organometallic reagent. However, after derivatisation to the
corresponding Weinreb Amide, reaction with organometallics does give the
desired ketones, as the initial adduct is stabilized and doesn't undergo
further reaction.

Mechanism of the Weinreb Ketone Synthesis

With the usual reaction of organometallic reagents with acid derivatives
(ester or acid chloride), the starting materials can add two equivalents of
organometallic compound. The ketone generated after the first addition is quite
reactive, and there is quite no selectivity between it and the starting acid
derivative:

The organometallic adducts of Weinreb Amides are able to form stable
chelates, and do not regenerate an electrophilic carbonyl group
in situ for further reaction: